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Am Fam Physician. 1998;58(8):1845-1847

Diabetic nephropathy is now the leading cause of renal failure in the Western world. Cooper reviews the natural history of diabetic nephropathy and discusses interventions that may prevent its development and progression.

The initial changes of glomerular hyperfiltration and hyperperfusion are followed by the development of subtle morphologic changes, including thickening of the glomerular basement membrane, glomerular hypertrophy and mesangial expansion. The first clinically detectable indication of incipient diabetic neuropathy is microalbuminuria, which manifests only after these changes are well established. Microalbuminuria is accompanied by other signs of diabetic microvascular damage and a modest rise in blood pressure (about 3 mm Hg per year). If untreated, the condition progresses to overt proteinuria and, eventually, to renal failure.

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Although the basic process is believed to be glucose-induced tissue injury, hypertension and other factors exacerbate renal damage. Genetic factors may play a role through variations in the reninangiotensin system that may mediate renal injury. A family history of hypertension has been linked with an increased risk of diabetic nephropathy.

The prevention and management of diabetic nephropathy is based on control of blood glucose levels and hypertension. Early studies showed benefits from tight glycemic control only before the stage of microalbuminuria. More recent studies, however, have reported reduced progression of renal impairment, even in proteinuric patients, when glycemic control was improved. While studies have conclusively demonstrated that control of blood pressure delays the onset of renal failure, the optimal therapy remains controversial.

Patients with type 1 (formerly known as insulin-dependent, or IDDM) diabetes mellitus and microalbuminuria should be treated with angiotensin converting enzyme (ACE) inhibitors even if the blood pressure is normal; studies have confirmed the renoprotective effect of these drugs. Some experts now advocate the use of ACE inhibitors even in the absence of microalbuminuria, because as many as 40 percent of patients with type 1 diabetes eventually develop nephropathy. Although early studies have shown benefits from early use of ACE inhibitors, more evidence is needed before this recommendation is widely advocated.

As shown in the accompanying algorithm, other classes of antihypertensive drugs may be required to maintain blood pressure control and to keep urinary protein excretion in target ranges. Patients receiving the combination of a calcium channel blocker (verapamil or nifedipine) and an ACE inhibitor have shown an improvement in renal function that may signify a delay in the development of diabetic nephropathy.

The role of dietary protein restriction for the prevention of diabetic nephropathy is not clear. Meta-analysis of data on the effects of dietary protein restriction in patients with diabetes suggests that protein restriction may have a beneficial effect on glomerular filtration rate, creatinine clearance and albuminuria. Long-term studies are needed to establish the efficacy of protein restriction. Problems with compliance, however, may limit this approach.

The importance of periodically screening for microalbuminuria in patients with diabetes is now clearly established. Early therapy with ACE inhibitors, particularly in hypertensive patients, has been proved to delay the onset of diabetic neuropathy and may reduce the risk of cardiovascular and retinal complications. The author emphasizes that screening and early therapy are potentially life-saving and can provide incalculable benefits to patients with diabetes.

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Copyright © 1998 by the American Academy of Family Physicians.

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